Objective: To investigate the relationship of hormone-sensitive adenylate cyclase and of cyclic AMP and cyclic GMP to regulatory processes in malignant cells, to the process of malignant transformation, and to cell dedifferentiation. Approach: Studies of adenylate cyclase in malignant and related normal cells cultured in vitro include relations to growth and cell cycle, influence of contact inhibition of growth, as well as the effects of transformation of normal cells by carcinogens and virus. Cell types include those of hepatic, connective tissue and lymphoid origin. Also included are studies of lens and kidney epithelial cell cultures. Tumors produced in vivo by virus and chemicals will be studied both directly in vivo and with malignant and premalignant cells cultured subsequently in vitro. Adenylate cyclase levels and hormonal activation, cyclic AMP levels and rates of degradation, cyclic nucleotide-dependent protein kinase levels, and influence of hormones on macromolecular synthesis and other metabolic processes will be studied. Cyclic GMP as possible mediator of cell proliferation, or as a possible "second messenger" for the effects of growth-promoting factors will be studied in malignant cells in culture. The adenylate cyclase system represents a control system which may provide a meaningful index of the functional state of a particular cell type. The presence of hormone receptors and growth control mechanisms involving cyclic nucleotides in malignant cells may provide systems capable of pharmacological manipulation and hence may ultimately be of therapeutic interest.